This Is MS Multiple Sclerosis Community: Knowledge & Support

Welcome to the world's leading forum on Multiple Sclerosis research, support, and knowledge. For over 10 years, This is MS has provided an unbiased community dedicated to Multiple Sclerosis patients, caregivers, and affected loved ones.

Advertisement

My husband is going to his DR next month. We intend to tell her that he is very interested still in the Tysabri treatment. I'll let you all know what she says, if we don't hear something else along the way.

That link was yet another business world press release trying to speculate on investing in Elan or Biogen. Those usually appear every few weeks with a spin from Biogen or Elan making some positive type comment on what is going on with the drug. The latest info is that after reviewing 2000 patients, there is no further confirmed cases of PML. One doc made the comment that the release said "no confirmed cases" as opposed to "no suspected further cases".

Another MS researcher (a paid spokesperson for Serono) stated that there were no spinal taps done on these patients so the results can't be considered conclusive! Not surprising to hear a comment like that from the competition.

The FDA was asked about their opinion about this information and again reiterated that they would not say anything until they were presented with all the new complete reviewed data. I heard that they may ask Biogen/Elan to conduct further safety trials but that is a rumor.

So, nothing has really changed with Tysabri and it won't until the FDA conducts its review. I've read on a couple of other MS forums that some patients' neuros when asked, stated that they would not prescribe Tysabri unless it was an absolute last resort.

You suggested that I should try some of that stuff.....geez Bromley, I don't think I would give that to my cat even if it ate one of those poor MS mice with EAE And you think I don't like Tysabri....you should see how my wife, who has had MS for 35 years, reacts when I mention it

Came across this article today which is quite interesting. Unless I'm wrong in understanding what is said, the JVC virus and thus PML is not caused by simply having inflammation in the CNS but by immunosuppresion alone or with other factors (Tysabri?) being involved.

Since this information was available in 1998, surely Biogen/Elan must have known something about the dangers of using immune suppressing drugs in combination with a monoclonal antibody such as Tysabri with MS patients.

JC virus (JCV) DNA was detected in cerebrospinal fluid (CSF) samples from patients with progressive multifocal leukoencephalopathy (PML) but not in CSF samples from patients with herpes simplex encephalitis, enteroviral meningitis, or multiple sclerosis. This suggests that inflammatory processes in the brain do not necessarily reactivate JCV, which further supports the proposal that the presence of JCV DNA in the CSF is diagnostic for PML.

Progressive multifocal leukoencephalopathy (PML) is a rare disease observed in immunosuppressed patients previously infected with JC virus (JCV) (15). In PML, JCV lytically infects myelin-producing oligodendrocytes. This leads to severe neurological symptoms and mental deterioration in the affected patients, and the disease has a lethal outcome (11). The precise mechanism of JCV reactivation in PML is not known, but one possibility is that JCV persisting in the brain after primary infection may be reactivated (4, 13, 19). A definite diagnosis of PML requires detection of JCV in brain tissue obtained by brain biopsy, and this is not readily performed. Recently, it has been shown that it is possible to detect JCV in the cerebrospinal fluid (CSF) from patients with PML (confirmed by brain biopsy) by using a JCV-specific PCR (5, 9, 12, 18]. Thus, JCV replicating in the brain is also detected in the CSF, and the presence of JCV in CSF has been proposed to be diagnostic for PML (5, 9, 12, 18].
Nevertheless, the presence of JCV in CSF samples from patients with other pathological conditions in the central nervous system (CNS) has not been examined extensively. It is not known if a latent virus like JCV possibly present in the brain could be activated during an inflammatory process in the CNS caused by other viruses. Furthermore, the possibility that JCV, which can cause demyelination in the brain, may also replicate in the brains of multiple sclerosis (MS) patients has not yet been completely excluded. To determine if JCV is activated in the brain during other viral infections in the CNS, or in MS, we examined CSF samples from patients with herpes simplex virus type 1 (HSV-1) encephalitis, enteroviral and nonenteroviral meningitis, and MS for the presence of JCV DNA.
Forty-three CSF samples from 39 patients with HSV-1 encephalitis, 20 CSF samples from 20 patients with enteroviral meningitis, and 15 CSF samples from 15 subjects with nonenteroviral meningitis were assayed for the presence of JCV DNA. In addition, 58 centrifuged CSF samples (45 samples collected during an exacerbation and 13 samples collected during remission) from 45 patients with early MS were also examined for the presence of JCV DNA. As positive controls, CSF samples previously described as JCV DNA positive from four AIDS patients with clinical and histopathological diagnoses of PML were used (9) .
The diagnosis of HSV-1 encephalitis in all 39 patients examined was confirmed by an HSV-1 DNA-specific nested PCR (1) . HSV-1 DNA was present in the CSF of all 39 patients, as indicated in Table 1. CSF samples from 35 patients (ages, 1 month to 67 years) with aseptic meningitis were examined by virus isolation for the presence of enterovirus infection (6), and 29 of these CSF samples were also examined by an enteroviral RNA-specific PCR (3, 7) . Eighteen of the 35 CSF samples were positive by virus isolation, and of the 18, 15 were tested and found positive with an enterovirus-specific RNA PCR (3, 7). The isolated enterovirus types, determined by a complement fixation test for 18 patients ( 8 ) , were ECHO 9 (2 patients) , ECHO 11 (2 patients) , ECHO 25 (1 patient), ECHO 30 (7 patients), Coxsackie B3 (1 patient), Coxsackie B4 (1 patient), and Coxsackie B5 (4 patients) . Of the remaining 17 patients, whose CSF samples were negative by enterovirus isolation, 14 were tested with an enteroviral PCR. Two of these were enterovirus RNA positive, and 12 remained negative. In summary, 20 of 35 patients with aseptic meningitis had confirmed enteroviral infections by culture (6) and/or PCR (7) .

. Asence of JCV DNA in CSF samples from patients with HSV-1 encephalitis

The 45 MS patients (ages, 21 to 55 years) had laboratory-supported diagnoses of definite MS or clinically definite MS (16) and were rated according to an expanded disability status scale (10). The patients were ambulatory and had expanded disability status scale scores of <4 (10), and they had suffered from MS between 5 days and 5 years (median, 4 months). CSF samples were collected within 4 weeks after an exacerbation, defined as a sudden appearance of MS-related symptoms and signs or worsening of previous findings lasting more than 24 h. Routine CSF examinations revealed mononuclear pleocytosis (>5 × 106 cells/liter) in 21 patients (47%) and oligoclonal immunoglobulin G bands in only the CSF in all patients (14). None of the patients had been treated with immunosuppressive or antiviral drugs, including corticosteroids and beta interferon.
All CSF specimens were stored at 20 or 70°C before testing. Each CSF sample was divided into 10-µl duplicates and heated at 95°C for 10 min before undergoing PCR. As a positive control, a CSF sample containing JCV DNA from a patient with PML from a previously described study was used (9), as well as unheated urine samples (1 to 5 µl) from organ transplant patients which contained JCV DNA or BK virus (BKV) DNA. A nested PCR specific for the early regions of both JCV and BKV was used in this study (2). Since JCV has 75% genome homology with BKV, another human polyomavirus, the JCV (173-bp) and BKV (176-bp) amplification products were distinguished by BamHI restriction enzyme cleavage. Only the JCV DNA amplimer was cleaved into two fragments (120 and 53 bp long) (2). The sensitivity of the PCR assay was 10 genome copies for both of the viruses.
All 43 CSF specimens (sampled between day 1 and more than 1 week after the onset of symptoms) from the 39 patients with HSV-1 encephalitis confirmed by an HSV-1-specific PCR technique (1) were negative for JCV DNA (Table 1). Furthermore, no JCV DNA could be detected in the CSF specimens from the 20 patients with confirmed enteroviral meningitis or from the 15 patients with meningitis of unknown etiology. In addition, no JCV DNA could be detected by PCR in the CSF specimens of the 45 patients with definite early MS. As expected, JCV DNA was present in the CSF samples of the four patients with PML (data not shown).
In summary, as in our previously published study (9), we could detect JCV DNA in the CSF samples from patients with PML. However, JCV DNA was not detected in CSF samples from patients with HSV-1 encephalitis, enteroviral or nonenteroviral meningitis, or MS. Our findings thus further support the proposal that detection of JCV DNA in the CSF is diagnostic for PML. Since the seroprevalence of JCV is around 75% (17), we had assumed it would be possible to detect JCV DNA in the CSF if JCV was indeed reactivated in the brains of patients with HSV-1 encephalitis, enteroviral meningitis, aseptic meningitis of unknown etiology, or MS. However, this was not the case. Our results therefore indicate that inflammation in the brain observed during the conditions listed above does not necessarily cause reactivation of JCV. Thus, in order to achieve an activation of JCV in the brain and to cause PML, immunosuppression alone or in combination with other unknown factors rather than simply an inflammation in the CNS is necessary. ACKNOWLEDGMENTS
This work was supported by the Karolinska Institute.

Dr. Lawrence Steinman wrote a very detailed article on Tysabri this past June. Although he discloses that he has a financial interest in a competitive company to Biogen, it is a very informative article and good reading.

I've transformed the article into an 11 page Word document. It is too long to post here but if you would like me to send you the file, please e-mail me at hzanin@rogers.com

Who is online

This site does not offer, or claim to offer, medical, legal, or professional advice.
All treatment decisions should always be made with the full knowledge of your physicians.
This is MS does not create, endorse, or republish any content.
All postings are the responsibility of the poster. All logos and trademarks in this site are property of their respective owners. All users must respect our rules for intellectual property rights.